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Background <p>Different colorectal cancer (CRC) studies rarely report overlapping prognostic genes. This study aimed to investigate the effects of sample size on prognostic genes analysis in CRC.</p> Methods <p>We included 418 CRC cases detected by whole-exome sequencing (WES) in the TCGA PanCancer cohort and 931 CRC cases detected by targeted sequencing in the MSK cohort. Prognostic genes analysis was repeated 200 times at each sample size level using a random resampling method.</p> Results <p>For WES data, the number of prognostic genes increased in a power-law with increasing sample size in CRC cases with stage III and IV. This pattern also applied to CRC patients with stage II after the removal of patients with MSI-H or <i>POLE</i> mutations. However, for targeted sequencing data, the number of prognostic genes increased linearly with increasing sample size in CRC cases with stage III and IV. About 550 cases were required for stage IV CRC to reach the plateau of prognostic genes. In both cohorts, the proportion of true prognostic genes relative to sample size was consistent with a binomial distribution, indicating a significant effect of sample size on the reliability of prognostic genes. At the same sample size level, the number of prognostic genes from the WES data was higher than that from the targeted sequencing data, while the reliability of prognostic genes from the WES data was lower.</p> Conclusion <p>This study shows the relationship between the number of prognostic genes and sample size in CRC and how mutation data affects this relationship. This will contribute to the trial design for prognostic genetic analysis in CRC.</p>

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Sample size required for prognostic genes analysis in colorectal cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年2月19日

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  • Chuanhua Zhao,
  • Xiao Lou,
  • Weilu Jia,
  • Zhiyi Wan,
  • Xin Lu,
  • Yuxuan Qiu,
  • Qianru Xu,
  • Kaiyu Jian,
  • Hongyan Zhang,
  • Feng Liang

摘要

Background

Different colorectal cancer (CRC) studies rarely report overlapping prognostic genes. This study aimed to investigate the effects of sample size on prognostic genes analysis in CRC.

Methods

We included 418 CRC cases detected by whole-exome sequencing (WES) in the TCGA PanCancer cohort and 931 CRC cases detected by targeted sequencing in the MSK cohort. Prognostic genes analysis was repeated 200 times at each sample size level using a random resampling method.

Results

For WES data, the number of prognostic genes increased in a power-law with increasing sample size in CRC cases with stage III and IV. This pattern also applied to CRC patients with stage II after the removal of patients with MSI-H or POLE mutations. However, for targeted sequencing data, the number of prognostic genes increased linearly with increasing sample size in CRC cases with stage III and IV. About 550 cases were required for stage IV CRC to reach the plateau of prognostic genes. In both cohorts, the proportion of true prognostic genes relative to sample size was consistent with a binomial distribution, indicating a significant effect of sample size on the reliability of prognostic genes. At the same sample size level, the number of prognostic genes from the WES data was higher than that from the targeted sequencing data, while the reliability of prognostic genes from the WES data was lower.

Conclusion

This study shows the relationship between the number of prognostic genes and sample size in CRC and how mutation data affects this relationship. This will contribute to the trial design for prognostic genetic analysis in CRC.